Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer
Throughout the United States and the world, skin cancer is the most frequent form of cancer. Sonidegib (SNG) is a hedgehog inhibitor that has been used for skin cancer treatment. However, SNG has low bioavailability and is associated with resistance. The focus of this work is to enhance bioavailabil...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/10/1560 |
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| author | Amr Gamal Haitham Saeed Fatma I. Abo El-Ela Heba F. Salem |
| author_facet | Amr Gamal Haitham Saeed Fatma I. Abo El-Ela Heba F. Salem |
| author_sort | Amr Gamal |
| collection | DOAJ |
| description | Throughout the United States and the world, skin cancer is the most frequent form of cancer. Sonidegib (SNG) is a hedgehog inhibitor that has been used for skin cancer treatment. However, SNG has low bioavailability and is associated with resistance. The focus of this work is to enhance bioavailability, anti-tumor efficacy and targeting of SNG via developing ethosome gel as a potential treatment for skin cancer. SNG-loaded ethosomes formulation was prepared and characterized in vitro by %entrapment efficiency (%EE), vesicle size, morphology, %release and steady-state flux. The results showed that the prepared formulation was spherical nanovesicles with a %EE of 85.4 ± 0.57%, a particle size of 199.53 ± 4.51 nm and a steady-state flux of 5.58 ± 0.08 µg/cm<sup>2</sup>/h. In addition, SNG-loaded ethosomes formulation was incorporated into carbopol gel to study the anti-tumor efficacy, localization and bioavailability in vivo. Compared with oral SNG, the formulation showed 3.18 times higher relative bioavailability and consequently significant anti-tumor activity. In addition, this formulation showed a higher rate of SNG penetration in the skin’s deep layers and passive targeting in tumor cells. Briefly, SNG-loaded ethosome gel can produce desirable therapeutic benefits for treatment of skin cancer. |
| first_indexed | 2024-03-10T06:17:39Z |
| format | Article |
| id | doaj.art-d999672fcdb8405f81cc339561f3c73a |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T06:17:39Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d999672fcdb8405f81cc339561f3c73a2023-11-22T19:37:33ZengMDPI AGPharmaceutics1999-49232021-09-011310156010.3390/pharmaceutics13101560Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin CancerAmr Gamal0Haitham Saeed1Fatma I. Abo El-Ela2Heba F. Salem3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 625617, EgyptClinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 625617, EgyptDepartment of Pharmacology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 625617, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 625617, EgyptThroughout the United States and the world, skin cancer is the most frequent form of cancer. Sonidegib (SNG) is a hedgehog inhibitor that has been used for skin cancer treatment. However, SNG has low bioavailability and is associated with resistance. The focus of this work is to enhance bioavailability, anti-tumor efficacy and targeting of SNG via developing ethosome gel as a potential treatment for skin cancer. SNG-loaded ethosomes formulation was prepared and characterized in vitro by %entrapment efficiency (%EE), vesicle size, morphology, %release and steady-state flux. The results showed that the prepared formulation was spherical nanovesicles with a %EE of 85.4 ± 0.57%, a particle size of 199.53 ± 4.51 nm and a steady-state flux of 5.58 ± 0.08 µg/cm<sup>2</sup>/h. In addition, SNG-loaded ethosomes formulation was incorporated into carbopol gel to study the anti-tumor efficacy, localization and bioavailability in vivo. Compared with oral SNG, the formulation showed 3.18 times higher relative bioavailability and consequently significant anti-tumor activity. In addition, this formulation showed a higher rate of SNG penetration in the skin’s deep layers and passive targeting in tumor cells. Briefly, SNG-loaded ethosome gel can produce desirable therapeutic benefits for treatment of skin cancer.https://www.mdpi.com/1999-4923/13/10/1560skin cancerSonidegibethosomestargetingbioavailability |
| spellingShingle | Amr Gamal Haitham Saeed Fatma I. Abo El-Ela Heba F. Salem Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer Pharmaceutics skin cancer Sonidegib ethosomes targeting bioavailability |
| title | Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer |
| title_full | Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer |
| title_fullStr | Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer |
| title_full_unstemmed | Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer |
| title_short | Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer |
| title_sort | improving the antitumor activity and bioavailability of sonidegib for the treatment of skin cancer |
| topic | skin cancer Sonidegib ethosomes targeting bioavailability |
| url | https://www.mdpi.com/1999-4923/13/10/1560 |
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